Butyrate and beta-hydroxybutyrate compositions

ABSTRACT

Compositions and methods for providing a person with an exogenous and therapeutically effective supply of ketones are disclosed. The compositions may consist essentially of (a) purified butyrate (or esters or propionate salts thereof) and (b) purified beta-hydroxybutyrate (or esters or propionate salts thereof). The compositions may further include other pharmacologically active agents, such as acetyl-L carnitine, R-alpha lipoic acid, green tea extract, vitamins, and various combinations of such agents. The methods include providing a person with an exogenous supply of ketones, by orally administering a pharmacologic composition, which is effective to deliver 2000-5000 mg of a short chain fatty acid (e.g., butyrate) and 5000-10,000 mg of ketone (e.g., beta-hydroxybutyrate) on a daily basis.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/187,823, filed Jun. 21, 2016, which claims priority to, andincorporates by reference, U.S. provisional patent application Ser. No.62/317,607, filed on Apr. 3, 2016.

FIELD OF THE INVENTION

The field of the present invention relates to certain compositions thatcomprise a combination of short chain fatty acids (such as butyrate) andketones (such as beta-hydroxybutyrate), which provide the various healthbenefits described herein.

BACKGROUND OF THE INVENTION

Ketones (Background)

It is well understood that dietary restriction in the form of caloriedeprivation and/or a low carbohydrate/high fat diet (LCHFD) is conduciveto ketogenesis. Although hyperketonemia (>0.5 mmol/L of serum ketones),when induced by such dietary programs, has been shown to producepositive effects on biological markers of insulin resistance, serumglucose stabilization, diabetes, obesity, epilepsy, cognitive deficits,inflammation and even cancer, achievement and sustenance of functionalserum ketone levels is a very difficult task. Achieving a state ofketosis requires dedication and sacrifice, while enduring states ofmalaise during energy substrate transition. For some, the achievement ofketosis is more difficult than for others based on metabolic, genetic,environmental, and lifestyle factors combined.

Sustained ketosis is also a state desired by athletes in pursuit ofimproved performance, as a function of ketones serving as substrates formitochondrial ATP generation. Research shows that ketones produce asmuch as 38% more ATP per unit carbon than glucose as substrates of theTCA cycle. In addition, research shows ATP generation from ketones assubstrates in the mitochondria instead of glucose results in fewer freeradical by-products. Furthermore, ketones are shown to inducetranscription and subsequent synthesis of endogenous antioxidants,thereby priming the generation of intracellular glutathione and otherendogenous antioxidants to produce a proactive protection againstoxidative stress.

Athletes in ketosis and under physical load are shown to operate at fullpower output with a lower VO2 max than those utilizing glucose(carbohydrate) as a primary source of ATP. When at elevated serum levelsindicative of ketosis, ketones are also known to spare muscle(anticatabolic) when under stress, including stress caused by nutrientdeprivation. Although ketosis is a metabolic state that does not fitoptimally for everyone who attempts to achieve it, there arepharmacological benefits of ketones, such asbeta-hydroxyl-butyrate/beta-hydroxybutyrate (BHB) and acetoacetate whenthey exist in hyperketonemic states. Healthy ketosis is represented by astate where ketones measure in the range 0.4-5.0 mmol/L, while bloodsugar remains stable and at around baseline of 4.2-5.0 mmol/L.

Although it is known that ketones serve as substrates for efficient ATPgeneration, the means by which such ketones also serve as ligands forvarious receptors, such as hydroxyl carboxylic acid receptors (HCA), arenot well understood. BHB is a known HCA2 receptor agonist and,therefore, it is expected to have some neuroprotective activity,vis-à-vis its activity on monocytes and macrophages.

During carbohydrate deprivation, serum glucose declines and themetabolism can shift to fatty acid beta-oxidation and the production ofketones. This is the essence of endogenous ketone induction. Althoughfatty acids cannot readily cross the blood brain barrier to serveneurons as an energy substrate amid carbohydrate deprivation, ketonesare hydrophilic and can cross to serve efficiently as substrates forneuron ATP generation. Ketones can supply in excess of 50% of thebrain's energy requirements during periods of glucose scarcity. Thescarcity of glucose amid the abundantly available ketone causes cells toincrease mitochondrial numbers, induce endogenous antioxidantgeneration, and activate various other protective mechanisms.

It has further been established that many neurological disorders areassociated with impaired mitochondrial activity, compromisedmitochondrial numbers, limited endogenous antioxidant status, elevatedfree radical generation, and oxidation amongst other pathologicalfeatures and hallmarks. Ketosis has been shown to improve many of thesepathological features.

In view of the foregoing, the exogenous supply of ketones may offer anumber of pharmacological benefits, including both mental and physicalbenefits. A daily supply of exogenous ketones would alleviate the stressassociated with diet adherence, and would allow for the pharmacologicalbenefits of ketones to continue due to the maintenance of elevated serumketone levels (despite the temporary or prolonged increment of serumglucose and stored glycogen that may ensue as a function of a meal orfew days off a ketogenic cycle). An exogenous supplement of ketoneswould also provide an immediate and efficient transition back to aketogenic lifestyle, without the associated energy deficit that istypically associated with the cell-switch-back to serum ketones and fatas an energy (ATP) substrate. Metabolic support during energy substratescarcity would be another substantial benefit of an exogenous ketonesupply, particularly in the context of calorie or carbohydratedeprivation for weight management or therapy of other types. Anexogenously supply of ketones would further serve as a bridging energysource during a low-carbohydrate diet and fluctuations in dietaryhabits, whether those shifts are long-term initiatives or short-termbreaks. An exogenous supply of ketones would serve to avert the state ofmalaise that is often attendant to a calorie/carbohydrate deprivedstate, and would improve appetite control and support cognitivealertness.

Butyrate (Background)

Short chain fatty acids, also known as volatile fatty acids, are thosetypically produced by the microbial community of the intestine. Thesemicrobes are often referred to as probiotics or microbiota. Suchmicrobes comprise a significant component of the immune system. Thesesymbiotic microbes produce short chain fatty acids from dietary fiber,i.e., fatty acids that serve as signaling ligands for various receptorsinvolved in inflammatory control, including the HCA2 receptor (the abovedescribed beta-hydroxybutyrate (ketone) serves as an agonist for suchreceptor as well).

The short chain fatty acids of the intestinal lumen include mostabundantly, butyrate, propionate, and acetate. Research shows thatbutyrate fed mice remain lean (despite dietary calorie load); avoidmetabolic problems; have increased energy expenditure in the form ofbody heat generation; and tend to have higher physical activity.Butyrate has been shown to lower serum cholesterol in various studiesand by as much as 25% in some studies, and reduce serum triglycerides byas much as 50% compared to controls. Butyrate has further been shown tolower fasting insulin by nearly 50%, and increase insulin sensitivity byas much as 300%. Still further, butyrate administration has been shownto improve appetite and food portion control.

Research has further shown that butyrate is a key fuel for epithelialcells of the intestinal tract and that it may improve gut liningintegrity. Similar to BHB, butyrate is an inhibitor of HDAC to induceglobal changes in genetic transcription of genes encoding oxidativestress resistance. This down regulation of gene transcription results inimproved protection from free radical damage associated with strained orextreme metabolic conditions (and environmental toxins). This geneticoptimization provided by butyrate also includes neuroprotection, similarto that exhibited by BHB.

Still further, lumen butyrate has been shown to directly preserve gutfriendly bacteria in the microbiota, while adversely affectingpathogenic bacteria like Escherichia coli, Salmonella spp. andCampylobacter spp. Passive absorption of water in the colon depends onshort chain fatty acid availability. Butyrate has been shown to play arole in healthy peristalsis to help normalize movement in cases ofconstipation or diarrhea. Butyrate serves to support optimal hydrationand optimal bowel elimination function. Butyrate has also been shown toexhibit trophic effects on intestinal cell proliferation, improvingvilli, and general lining health. In addition, butyrate has been shownto be a potent promoter of intestinal regulatory T cells establishingyet another immune regulating mechanism that promotes betterinflammatory control at the mucosal lining. Promotion ofgastrointestinal health provides a formidable platform for improvedgeneral and systemic health.

To compound the benefits offered by ketosis (as described above), it isknown from the literature that butyrate induces FGF21 in serum, liverand adipocytes, which in turn stimulates fatty acid oxidation andhepatic ketone production. This serves as an inducing signal forketosis, along with butyrate itself, thereby serving as a directsubstrate for ketone production and energy generation. In short,butyrate serves as a significant synergistic force for ketosisinduction; BHB ligand interactions and pharmacology; and general health,fitness and performance support.

As discussed above, an exogenous supply of ketones, such as BHB, willprovide an immediate alternative energy (ATP) source during periods ofcalorie or carbohydrate deprivation. However, concurrent butyratesupplementation in the form of sodium, calcium or potassium butyrate (orits esters) will prompt the body to induce endogenous ketone synthesis;will serve as a ligand to stimulate receptors that the ketone will acton; will contribute to the improvement of insulin and general metabolichealth; will support inflammatory and general immune system health; willimprove gastrointestinal health and integrity—all in parallel with thebenefits that concurrent supplementation of the sister ketone moleculewill provide.

As the following will demonstrate, the compositions and methods of thepresent invention will be very useful for providing an exogenous supplyof ketones, to provide a person with the numerous pharmacologic benefitsdescribed herein.

SUMMARY OF THE INVENTION

According to certain aspects of the invention, compositions are providedthat include combinations of short chain fatty acids (e.g., butyrate)and ketones (e.g., beta-hydroxybutyrate), and/or derivatives of theforegoing. The compositions of the present invention offer a multitudeof benefits and can be used for numerous applications. For example, oralformulations of such compositions may be used for sustaining elevatedlumen and serum short chain fatty acid (SCFA) and/or ketoneconcentrations intended for therapeutic applications, such as body massalteration, support of insulin activity, and support of cognitiveactivity (despite probiotic (microbiome) status and diet). Moreparticularly, the compositions of the invention may be useful fortreating or preventing obesity, insulin resistance, metabolic syndromes,cognitive deficits, IBS, IBD, epilepsy, atrophy, and catabolism.

The above-mentioned and additional features of the present invention arefurther illustrated in the Detailed Description contained herein.

DETAILED DESCRIPTION OF THE INVENTION

The following will describe, in detail, several preferred embodiments ofthe present invention. These embodiments are provided by way ofexplanation only, and thus, should not unduly restrict the scope of theinvention. In fact, those of ordinary skill in the art will appreciateupon reading the present specification and viewing the present drawingsthat the invention teaches many variations and modifications, and thatnumerous variations of the invention may be employed, used and madewithout departing from the scope and spirit of the invention.

According to certain preferred embodiments of the present invention,compositions providing a person with an exogenous and therapeuticallyeffective supply of ketones are disclosed. In certain preferredembodiments, the compositions of the present invention may consistessentially of (a) purified butyrate (or esters or propionate saltsthereof) and (b) purified beta-hydroxybutyrate (or esters or propionatesalts thereof). The invention provides that the compositions may furtherinclude other pharmacologically active agents, such asacetyl-L-carnitine, R-alpha lipoic acid, green tea extract, vitamins,and various combinations of such agents.

The invention provides that acetyl-L-carnitine (a source of L-carnitinefollowing administration) has been shown to support cognition and mood;improve Alzheimer's symptoms; and support cardiovascular health. Theinvention provides that a composition of the invention that includesacetyl-L-carnitine will be designed to support mitochondrial fatty acidoxidation in the context of a low carbohydrate diet and ketosis. Theinvention provides that R-alpha lipoic acid will serve as an antioxidantand will support insulin sensitivity (i.e., to provide antioxidantprotection in fat and water mediums and improve serum glucose clearanceto facilitate ketosis and ketone prevalence as an energy substrate). Theinclusion of high-epigallocatechin gallate (EGCG) and high-caffeinegreen tea extract will provide a natural source caffeine to support betaoxidation of fatty acids and ketosis induction; it will supply asignificant amount of EGCG for optimal antioxidant support; and it willprovide anti-amylase activity to inhibit or slow carbohydrate digestionto result in an impaired glycemic index of and serum contribution bydietary carbohydrate sources, which promotes a ketogenic environment.

According to additional preferred embodiments of the present invention,methods for providing a person with an exogenous and therapeuticallyeffective supply of ketones are disclosed. In certain embodiments, themethods generally include providing a person with an exogenous supply ofketones (or precursors thereof), by orally administering one of thepharmacologic compositions described herein, which is effective todeliver 1000-5000 mg of a short chain fatty acid (e.g., butyrate) and1000-10,000 mg of ketone (e.g., beta-hydroxybutyrate) or, morepreferably, which is effective to deliver 2000-5000 mg of butyrate and5000-10,000 mg of beta-hydroxybutyrate to a person on a daily basis. Asdescribed further below (and in the Examples), such compositions may bepreferably delivered to a person in the form of oral capsules or drypowders.

Notwithstanding the preferred embodiments and Examples described herein,the invention provides that the compositions of the present inventionmay be administered in any desired and effective manner, e.g., aspharmaceutical compositions or nutritional supplements for oralingestion. More particularly, for example, pharmaceutically acceptablecompositions or nutritional supplements of the invention may compriseone or more of the compositions described herein with one or moreacceptable carriers. Regardless of the route of administration selected,the compositions may be formulated into acceptable dosage forms byconventional methods known to those of skill in the art. For example,acceptable carriers include, but are not limited to, sugars (e.g.,lactose, sucrose, mannitol, and sorbitol), silicon dioxide, starches,cellulose preparations (such as microcrystalline cellulose), calciumphosphates (e.g., dicalcium phosphate, tricalcium phosphate and calciumhydrogen phosphate), sodium citrate, water, aqueous solutions, alcohols(e.g., ethyl alcohol, propyl alcohol, and benzyl alcohol), polyols(e.g., glycerol, propylene glycol, and polyethylene glycol), organicesters (e.g., ethyl oleate and tryglycerides), biodegradable polymers(e.g., polylactide-polyglycolide, poly(orthoesters), andpoly(anhydrides)), elastomeric matrices, liposomes, microspheres, oils(e.g., corn, germ, olive, castor, sesame, cottonseed, and groundnut),cocoa butter, waxes, paraffins, silicones, talc, silicylate, etc.

Each acceptable carrier used in a pharmaceutical composition ornutritional supplement of the invention must be “acceptable” in thesense of being compatible with the other ingredients of the formulationand not injurious to the subject. Carriers suitable for a selecteddosage form and intended route of administration are well known in theart, and acceptable carriers for a chosen dosage form and method ofadministration can be determined using ordinary skill in the art.

The pharmaceutical compositions and nutritional supplements of theinvention may, optionally, contain additional ingredients and/ormaterials commonly used in pharmaceutical compositions and/ornutritional supplements. These ingredients and materials include (1)fillers or extenders, such as starches, lactose, sucrose, glucose,mannitol, and silicic acid; (2) binders, such as carboxymethylcellulose,alginates, gelatin, polyvinyl pyrrolidone, hydroxypropylmethylcellulose, sucrose and acacia; (3) humectants, such as glycerol; (4)disintegrating agents, such as agar-agar, calcium carbonate, potato ortapioca starch, alginic acid, certain silicates, sodium starchglycolate, cross-linked sodium carboxy methyl cellulose and sodiumcarbonate; (5) solution retarding agents, such as paraffin; (6)absorption accelerators, such as quaternary ammonium compounds; (7)wetting agents, such as cetyl alcohol and glycerol monosterate; (8)absorbents, such as kaolin and bentonite clay; (9) lubricants, such astalc, calcium stearate, magnesium stearate, solid polyethylene glycols,and sodium lauryl sulfate; (10) suspending agents, such as ethoxylatedisostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters,microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agarand tragacanth; (11) buffering agents; (12) excipients, such as lactose,milk sugars, polyethylene glycols, animal and vegetable fats, oils,waxes, paraffins, cocoa butter, starches, tragacanth, cellulosederivatives, polyethylene glycol, silicones, bentonites, silicic acid,talc, salicylate, zinc oxide, aluminum hydroxide, calcium silicates, andpolyamide powder; (13) inert diluents, such as water or other solvents;(14) preservatives; (15) surface-active agents; (16) dispersing agents;(17) control-release or absorption-delaying agents, such ashydroxypropylmethyl cellulose, other polymer matrices, biodegradablepolymers, liposomes, microspheres, aluminum monosterate, gelatin, andwaxes; (18) opacifying agents; (19) adjuvants; (20) wetting agents; (21)emulsifying and suspending agents; (22), solubilizing agents andemulsifiers, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate,ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol,1,3-butylene glycol, oils (in particular, cottonseed, groundnut, corn,germ, olive, castor and sesame oils), glycerol, tetrahydrofuryl alcohol,polyethylene glycols and fatty acid esters of sorbitan; (23)propellants, such as chlorofluorohydrocarbons and volatile unsubstitutedhydrocarbons, such as butane and propane; (24) antioxidants; (25) agentswhich render the formulation isotonic with the blood of the intendedrecipient, such as sugars and sodium chloride; (26) thickening agents;(27) coating materials, such as lecithin; (28) vitamins and minerals;(29) proteins that carry therapeutic or nutritional benefits, such aswhey protein and other milk-derived proteins; and (30) sweetening,flavoring, coloring, perfuming and preservative agents. Each suchingredient or material must be “acceptable” in the sense of beingcompatible with the other ingredients of the formulation and notinjurious to the subject. Ingredients and materials suitable for aselected dosage form and intended route of administration are well knownin the art, and acceptable ingredients and materials for a chosen dosageform and method of administration may be determined using ordinary skillin the art.

Pharmaceutical compositions and nutritional supplements suitable fororal administration may be in the form of capsules, cachets, pills,tablets, powders, granules, a solution or a suspension in an aqueous ornon-aqueous liquid, an oil-in-water or water-in-oil liquid emulsion, anelixir or syrup, or a paste. These formulations may be prepared bymethods known in the art, e.g., by means of conventional pan-coating,mixing, granulation or lyophilization processes.

Solid dosage forms for oral administration (capsules, tablets, pills,powders, granules and the like) may be prepared by mixing the activeingredient(s) with one or more acceptable carriers and, optionally, oneor more fillers, extenders, binders, humectants, disintegrating agents,solution retarding agents, absorption accelerators, wetting agents,absorbents, lubricants, and/or coloring agents. Solid compositions of asimilar type may be employed as fillers in soft and hard-filled gelatincapsules using a suitable excipient. A tablet may be made by compressionor molding, optionally with one or more accessory ingredients.Compressed tablets may be prepared using a suitable binder, lubricant,inert diluent, preservative, disintegrant, surface-active or dispersingagent. Molded tablets may be made by molding in a suitable machine. Thetablets, and other solid dosage forms, such as capsules, pills andgranules, may optionally be scored or prepared with coatings and shells,such as enteric coatings and other coatings well known in the art. Thetablets, and other solid dosage forms, may also be formulated so as toprovide slow or controlled release of the active ingredient therein.They may be sterilized by, for example, filtration through abacteria-retaining filter. These compositions may also optionallycontain opacifying agents that release the active ingredient only, orpreferentially, in a certain portion of the gastrointestinal tract,optionally, in a delayed manner. The active ingredient can also be in amicroencapsulated form.

Liquid dosage forms for oral administration include acceptableemulsions, microemulsions, solutions, suspensions, syrups, and elixirs.The liquid dosage forms may contain suitable inert diluents commonlyused in the art. Besides inert diluents, the oral compositions may alsoinclude adjuvants, such as wetting agents, emulsifying and suspendingagents, sweetening, flavoring, coloring, perfuming and preservativeagents. Suspensions may contain suspending agents.

EXAMPLES Example 1

The following Example describes a composition of the present invention,which includes butyrate salts (and/or esters or propionate saltsthereof), in combination with beta-hydroxybutyrate salts (and/or estersor propionate salts thereof). In this Example, the target subject willpreferably receive, on a daily basis, 1000-5000 mg of a short chainfatty acid (e.g., butyrate) and 1000-10,000 mg of ketone (e.g.,beta-hydroxybutyrate)—or, more preferably, 2000-5000 mg of butyrate and5000-10,000 mg of beta-hydroxybutyrate. The invention provides thatadditional optimizing ingredients may be included in the formulation.For example, acetyl carnitine may be included, to provide a fatty acidtransport mechanism facilitator. In addition, R-alpha lipoic acid may beincluded to improve insulin efficacy and to drive serum glucose levelsdown to be conducive to ketogenesis and ketone body prevalence as an ATPsubstrate.

In the following Example, the invention provides that an approximate 2:1(butyrate:beta-hydroxybutyrate) ratio may be employed. Alternatively,the invention provides that a 1:1 ratio can also be used, or otherratios that are deemed suitable for the mode of delivery and the bodymass of the target subject (person). The following provides an exampleformulation of the compositions of the present invention, showing acapsule formulation (at 1:1 and 2:1 ratios of butyrate andbeta-hydroxybutyrate) and a powder formulation.

Capsules (1:1 Butyrate/Beta-Hydroxybutyrate Ratio)

Component Amount (mg) Butyrate Sodium Salt 100 Butyrate Calcium Salt 100Butyrate Magnesium Salt 100 Beta Hydroxybutyrate Sodium Salt 100 BetaHydroxybutyrate Calcium Salt 100 Beta Hydroxybutyrate Magnesium Salt 200Acetyl-L Carnitine 70 R alpha lipoic acid 12 Green Tea Extra (14%Caffeine) 70 Total per capsule 852

Capsules (2:1 Butyrate/Beta-Hydroxybutyrate Ratio)

Component Amount (mg) Butyrate Sodium Salt 50 Butyrate Calcium Salt 50Butyrate Magnesium Salt 100 Beta Hydroxybutyrate Sodium Salt 100 BetaHydroxybutyrate Calcium Salt 100 Beta Hydroxybutyrate Magnesium Salt 200Acetyl-L Carnitine 70 R alpha lipoic acid 12 Green Tea Extra (14%Caffeine) 70 Total per capsule 852

Powder Pouch/Canister

Component Amount (mg) Powdered Cream/Butter Powder 3000 CoconutFat/Cream Powder 2000 Butyrate Sodium Salt 1000 Butyrate Calcium Salt1000 Butyrate Magnesium Salt 1000 Beta Hydroxybutyrate Sodium Salt 1000Beta Hydroxybutyrate Calcium Salt 1000 Beta Hydroxybutyrate MagnesiumSalt 1000 Resistant Starch 10000 Agave Extract 2000 Stevia 90 BerryFlavor 1000 Vitamin B1 diphosphate 5 Vitamin B2 Riboflavin 5 Vitamin B2Riboflavin 5′-phosphate 5 Niacin B3 10 Niacinaminde B3 5 NADH B3 5Vitamin B5 panthenol 5 Vitamin B6 pyridoxine HCl 5 Vitamin B6 pyridoxine5′-phosphate 5 Vitamin B7 Biotin 0.5 Vitamin B9 Folic Acid 1 Vitamin B121 Inositol 0.3 Choline Bitartrate 0.3 Acetyl-L Carnitine 700 R alphalipoic acid 12 Green Tea Extra (14% Caff total) 70 Total 24,843

Example 2

The following Example describes another composition of the presentinvention, which includes butyrate salts (and/or esters or propionatesalts thereof), in combination with beta-hydroxybutyrate salts (and/oresters or propionate salts thereof). In this Example, the compositionwas formulated as individual capsules, which comprised the componentsset forth in the table below.

Component Amount (mg)/% Total Calcium Butyrate Powder  50 (8.0%)Magnesium Butyrate Powder 150 (23.8%) Sodium Beta Hydroxybutyrate Powder102 (16.2%) Magnesium Beta Hydroxybutyrate Powder 306 (48.6%) Other(Magnesium Stearate; Silicon  22 (3.4%) Dioxide; Capsule Vegetable Oil)Total 630 (100%)

Example 3

The capsule described in Example 2 was administered to a male subject,49 years of age with a body weight of 190 pounds, who exhibitedabove-average fitness. The subject was administered a total of five (5)capsules at time=0 (following approximately four (4) hours of fasting),and the subject's serum glucose and serum ketone levels weresubsequently measured at the time points listed in the table below.

Time (Minutes/Post-Admin) 0 15 30 45 60 Serum Glucose (mM/L) 4.3 4.1 4.24.6 4.7 Serum Ketone (mM/L) 0.25 0.4 0.4 0.5 0.4

Example 4

In this Example, the capsule described in Example 2 was administered tothe male subject described in Example 3. The subject was administered atotal of eight (8) capsules at time=0 (following approximately twelve(12) hours of fasting), and the subject's serum glucose and serum ketonelevels were subsequently measured at the time points listed in the tablebelow.

Time (Minutes/Post-Admin) 0 15 45 60 75 90 105 Serum Glucose (mM/L) 4.75.3 5.6 5.4 5.6 6.0 4.9 Serum Ketone (mM/L) 0.2 0.2 0.4 0.4 0.4 0.2 0.2

Example 5

In this Example, the capsule described in Example 2 was administered tothe male subject described in Example 3. The subject was administered atotal of six (6) capsules at time=0 (following approximately three (3)hours of fasting), and the subject's serum glucose and serum ketonelevels were subsequently measured at the time points listed in the tablebelow.

Time (Minutes/Post-Admin) 0 15 30 45 60 75 Serum Glucose (mM/L) 4.5 4.14.8 4.9 4.2 4.2 Serum Ketone (mM/L) 0.2 0.2 0.3 0.4 0.3 0.2

As shown in Examples 3-5, a composition of the present invention waseffective to induce healthy ketosis in a subject (represented by a statewhere ketones are elevated), while maintaining a relatively stable bloodsugar level.

The many aspects and benefits of the invention are apparent from thedetailed description, and thus, it is intended for the following claimsto cover all such aspects and benefits of the invention that fall withinthe scope and spirit of the invention. In addition, because numerousmodifications and variations will be obvious and readily occur to thoseskilled in the art, the claims should not be construed to limit theinvention to the exact construction and operation illustrated anddescribed herein. Accordingly, all suitable modifications andequivalents should be understood to fall within the scope of theinvention as claimed herein.

What is claimed is:
 1. A composition comprising: (a) purified butyrateor esters or propionate salts thereof, wherein the purified butyrateincludes a butyrate sodium salt, a butyrate calcium salt, or a butyratemagnesium salt; and (b) purified beta-hydroxybutyrate or esters orpropionate salts thereof, wherein the purified beta-hydroxybutyrateincludes a beta-hydroxybutyrate sodium salt, a beta-hydroxybutyratecalcium salt, or a beta-hydroxybutyrate magnesium salt, wherein thecomposition is packaged in a form selected from the group consisting of(i) an oral capsule, (ii) in powdered form, (iii) in an aqueous ornon-aqueous liquid, (iv) in an oil-in-water or water-in-oil emulsion,(v) in an elixir or syrup, or (vi) in a paste, wherein the compositionis effective to deliver 1000- 5000 mg of a short chain fatty acid and1000-10,000 mg of ketone to a person on a daily basis.
 2. Thecomposition of claim 1, which further comprises an agent selected fromthe group consisting of acetyl-L carnitine, R-alpha lipoic acid, andgreen tea extract.
 3. The composition of claim 1, which furthercomprises one or more vitamins.
 4. The composition of claim 1, whichfurther comprises one or more preservatives.
 5. The composition of claim1, wherein the total purified butyrate to total purifiedbeta-hydroxybutyrate ratio is about 1:1.
 6. A method for providing aperson with an exogenous supply of ketones, by orally administering acomposition of claim 1 to the person, which is effective to deliver1000-5000 mg of a short chain fatty acid and 1000-10,000 mg of ketone ona daily basis.
 7. The method of claim 6, wherein the composition furthercomprises an agent selected from the group consisting of acetyl-Lcarnitine, R-alpha lipoic acid, and green tea extract.
 8. The method ofclaim 6, wherein the composition further comprises one or more vitamins.9. The method of claim 6, wherein the composition further comprises oneor more preservatives.
 10. The method of claim 6, wherein the totalpurified butyrate to total purified beta-hydroxybutyrate ratio is about1:1.
 11. The method of claim 6, wherein the total purified butyrate tototal purified beta-hydroxybutyrate ratio is about 2:1.